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Prefrontal lobe structural integrity and trail making test, part B: converging findings from surface-based cortical thickness and voxel-based lesion symptom analyses

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Abstract

Surface-based cortical thickness (CT) analyses are increasingly being used to investigate variations in brain morphology across the spectrum of brain health, from neurotypical to neuropathological. An outstanding question is whether individual differences in cortical morphology, such as regionally increased or decreased CT, are associated with domain-specific performance deficits in healthy adults. Since CT studies are correlational, they cannot establish causality between brain morphology and cognitive performance. A direct comparison with classic lesion methods is needed to determine whether the regional specificity of CT-cognition correlations is similar to that observed in patients with brain lesions. We address this question by comparing the neuroanatomical overlap of effects when 1) whole brain vertex-wise CT is tested as a correlate of performance variability on a commonly used neuropsychological test of executive function, Trailmaking Test Part B (TMT-B), in healthy adults and 2) voxel-based lesion-symptom mapping (VBLSM) is used to map lesion location to performance decrements on the same task in patients with frontal lobe lesions. We found that reduced performance on the TMT-B was associated with increased CT in bilateral prefrontal regions in healthy adults and that results spatially overlapped in the left dorsomedial prefrontal cortex with findings from the VBLSM analysis in patients with frontal brain lesions. Findings indicate that variations in the structural integrity of the left dorsomedial prefrontal lobe, ranging from individual CT differences in healthy adults to structural lesions in patients with neurological disorders, are associated with poor performance on the TMT-B. These converging results suggest that the left dorsomedial prefrontal region houses a critical region for the complex processing demands of TMT-B, which include visuomotor tracking, sequencing, and cognitive flexibility.

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Acknowledgments

This work was supported by Finding a Cure for Epilepsy and Seizures (FACES) and the Epilepsy Foundation (Targeted Research Initiative for Cognitive and Psychiatric Aspects of Epilepsy). The authors declare no competing financial interests.

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  1. Department of Neurology, Comprehensive Epilepsy Center, New York University School of Medicine, 145 East 32nd Street, #216, New York, NY, 10016, USA

    Nityanand Miskin, Thomas Thesen, William B. Barr, Tracy Butler, Xiuyuan Wang, Patricia Dugan, Ruben Kuzniecky, Werner Doyle, Orrin Devinsky & Karen Blackmon

  2. Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA

    Thomas Thesen

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Correspondence to Karen Blackmon.

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Supplementary Figure 1

Multislice coronal images of individual lesion masks are displayed on the standard MNI 152 template brain for visualization of lesion location. Patient numbers correspond to those listed in Table 2. (GIF 406 kb)

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Miskin, N., Thesen, T., Barr, W.B. et al. Prefrontal lobe structural integrity and trail making test, part B: converging findings from surface-based cortical thickness and voxel-based lesion symptom analyses. Brain Imaging and Behavior 10, 675–685 (2016). https://doi.org/10.1007/s11682-015-9455-8

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